Despite dramatic advances in combination chemoimmunotherapy for newly diagnosed patients with non-Hodgkin's lymphomas (NHL), few patients with relapsed B cell NHL can be cured with conventional treatments. The primary objective of this project is to optimize the therapeutic utility of high dose radiolabeled monoclonal antibodies targeting the CD20 antigen in conjunction with autologous stem cell transplant (ASCT) for treating patients with relapsed or refractory B cell lymphomas. In this application, we propose four approaches to achieve this goal. First, we will conduct a disease-specific, phase II trial of (131)I-anti-CD20 antibody with etoposide (VP16), cyclophosphamide (CY) and ASCT to establish the efficacy of this regimen for treating three of the most common histologic subtypes of relapsed B NHL (Aim I). Second, we will explore the ability of a synergistic chemotherapeutic agent (fludarabine) to enhance the efficacy of (131)I-anti-CD20 antibody for older patients in the setting of ASCT (Aim II). Third, we will investigate the feasibility and safety of improving the specificity of radiation dose delivery to tumor sites using pre-targeting technology (Aim III). Finally, we will perform long-term follow-up of patients treated on prior Phase I & II trials with (131)I-anti-CD20 antibodies + ASCT to ascertain long term efficacy and delayed toxicities (Aim IV). This sequence of studies should enable us to achieve our long term objectives of further establishing and augmenting the role of high dose radioimmunotherapy and ASCT in the treatment of relapsed NHL.